An investigation of the relationship between dietary antioxidants, lipid peroxidation and free radical events associated with the metabolism of carcinogenic compounds which promote lipid peroxidation in isolated liver cells is proposed. The tumorigenic activity of such carcinogens is inhibited by antioxidants and a study of the type described in this application may reveal an antioxidant-inhibited, free radical reaction which is obligatory for tumor formation. Current information indicates that the antioxidant content of diets relative to the polyunsaturated fatty acid content may have an important influence on tumor incidence. These two dietary components are antagonistic with respect to the occurrence of lipid peroxidation in tissues. Our current studies have shown that lipid peroxidation results in the formation of singlet oxygen (King, M.M., Lai, E.K., and McCay, P.B., J. Biol. Chem. 250: 6496, 1975) which could contribute to the activation of carcinogenic compounds which promote lipid peroxidation. We will employ spin-trapping compounds in these studies to observe free radical events during lipid peroxidation in isolated liver cells and subcellular fractions thereof. Spectra obtained from electron spin resonance (ESR) signals should permit analysis of the nature of the radical producing the signals. Preliminary studies have already indicated the feasibility of this approach. The function of the selenoenzyme, glutathione peroxidase, with respect to its influence on lipid peroxidation in membranes, is also included. Our current findings indicate that the enzyme does not operate to reduce lipid peroxidases in membranes as currently accepted. In view of the correlation between the selenium status of animals and tumor incidence, a study of the mechanism by which this enzyme inhibits lipid peroxidation in biological membranes is also proposed.